Diabetes mellitus is a disease that affects hundreds of millions of people worldwide and is characterized by loss of blood glucose control. This typically occurs through either autoimmune-mediated destruction of insulin-producing β cells found in islets of Langerhans within the pancreas or insulin resistance in peripheral tissue that leads to β cell failure. Common treatments for diabetes include insulin injections or drugs that either increase insulin sensitivity or increase insulin secretion from remaining β cells, but complications due to imprecise glucose control persist and are costly.
Replacement of insulin-producing β cells using stem cells (SC-β cells) is a promising approach for controlling diabetes in patients. There are currently no FDA-approved treatments using human pluripotent stem cells (hPSC), and the safety of any such hPSC-based product needs to be assured, which can be achieved with removal of the transplanted cells. Transplantation of β cells benefits from the ability of the β cell to survive and function when transplanted in non-pancreatic locations. Most current clinical approaches with cadaveric islets rely on infusion into the liver, rendering them irretrievable. Other transplantation sites used in research, such as the kidney capsule or fat pad, are not viable for clinical transplantation. Large spaces, such as subcutaneous, intraperitoneal, or in the omentum, can potentially hold a sufficiently large cell-embedded device to convey a positive clinical outcome while also allowing for cell retrieval. Furthermore, much of the prior research has been focused on cellular encapsulation, which prevents vascularization of the transplanted graft, which causes cellular hypoxia, as oxygen is only delivered to the cells through diffusion, leading to either necrosis or greatly reduced function of transplanted islets.
Therefore, there is a need for a macroporous device that allows vascularization of the device, improving survival and function and reducing delays in glucose sensing, which is biocompatible and degradable, to further promote β cell survival and function along with host integration and vascularization.